NEW HAVEN >> A new cancer treatment that acts like a nuclear-tipped missile aimed straight at tumor cells could be a breakthrough in treating a deadly form of lung cancer.

Planned clinical trials were given a boost from the Food and Drug Administration last week, when it approved a form of the treatment, called antibody-drug conjugates or, more vividly, armed antibodies, for "a very aggressive form of breast cancer," according to Dan Junius, CEO of ImmunoGen Inc. of Waltham, Mass., which developed the new therapy.

Now, Dr. Daniel Morgensztern, assistant professor of clinical oncology at Yale Medical School, is about to launch a clinical trial at the Smilow Cancer Hospital of a similar treatment for small-cell lung cancer. Accounting for about 13 percent of lung cancer cases, small cell is almost always caused by heavy smoking and "it's uniformly fatal in most cases," according to Dr. Roy Herbst, chief of medical oncology at Smilow.

The treatment of small-cell lung cancer "has not changed in about 25 years" and kills 25,000 to 30,000 people a year, he said.

Advertisement

The breast cancer drug is called Kadcyla and the new lung cancer drug is being created in a similar way. Herbst likens it to a rocket carrying a payload, but both the rocket and its poisonous baggage are deadly to cancer.

The "rocket" is an antibody -- in breast cancer's case Herceptin, a biologic therapy that accompanies chemotherapy. What ImmunoGen has been working on since 1996 is a way to bring an even more deadly drug into the tumor. The antibody-drug conjugates combine the two molecules with a "linker," as Morgensztern calls it. "It allows the drug to be delivered directly to the cancer cells," he said.

This is how it works:

The antibody binds with the cancer cell and is absorbed into it. But once inside, the antibody, the second poisonous agent and the linker break apart and the "smart bomb," called DM1, blows up the cancer cell. "It eats its own poison," Herbst said of the tumor.

A big advantage is that the treatment "allows the drug to be delivered directly to the cancer cells," reducing damage to normal tissue and the side effects that come with traditional chemotherapy, Morgensztern said.

"The ability to bring a poison to a target in a tumor cell, sparing a normal cell, is phenomenal," Herbst said.

The trick to creating the armed antibodies for different cancers is to find the toxin that will work best for each.

"We need to find that vulnerability, find what makes it unique ... target it, find it and then poison it," Herbst said.

In clinical trials of Kadcyla, the breast cancer drug, "the patients had a meaningful improvement in overall survival," said ImmunoGen's Junius. "Patients had a much better tolerance of the therapy" than with the alternative used.

Junius said there are nine other antibody-drug conjugates being developed for other cancers, such as ovarian, glioblastomas, non-small cell lung cancer, non-Hodgkin's lymphoma and a form of leukemia.

In Morgensztern's trial, which will involve 120 patients at six sites, one-third of patients will be given six treatments of traditional therapy over six weeks. The majority will receive the antibody-drug conjugates "until the cancer stops working," he said.

To apply to be a part of the trial, call Susan Porto at the Smilow Cancer Hospital Thoracic Oncology Program, 203-200-5864.